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排序方式: 共有10000条查询结果,搜索用时 46 毫秒
71.
Gloyn AL Reimann F Girard C Edghill EL Proks P Pearson ER Temple IK Mackay DJ Shield JP Freedenberg D Noyes K Ellard S Ashcroft FM Gribble FM Hattersley AT 《Human molecular genetics》2005,14(7):925-934
Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro. 相似文献
72.
Sadowy E Zhou J Meats E Gniadkowski M Spratt BG Hryniewicz W 《Microbial drug resistance (Larchmont, N.Y.)》2003,9(1):81-86
Multilocus sequence typing (MLST) of 35 isolates of multidrug-resistant Streptococcus pneumoniae recovered in Poland during 1995-1996 distinguished 10 different sequence types (ST). The majority of the isolates were assigned to two Polish clones of serotypes 6B and 23F, although the international clones, Spain23F-1 and Spain9V-3, were also identified. Similar results were obtained using pulsed-field gel electrophoresis (PFGE), providing a direct comparison of these two typing methods. 相似文献
73.
Kallen Michael A. Brown Heather E. Hatton Joeffrey R. Doyle William A. Murphy Ryan Elliott Ryan Gutierrez Mark A. Catherwood Emma L. Pitman Heather P. Liu Vincent X. Gershon Richard C. 《Quality of life research》2022,31(7):2201-2212
Quality of Life Research - To develop two item content-matched, precise, score-level targeted inpatient physical function (PF) short form (SF) measures: one clinician-reported, one... 相似文献
74.
Abrar M. Babateen Oliver M. Shannon Gerard M. OBrien Edward Okello Anmar A. Khan Sofia Rubele Emma Wightman Ellen Smith Nicholas McMahon Dilara Olgacer Christina Koehl William Fostier Inês Mendes David Kennedy John C. Mathers Mario Siervo 《Nutrients》2021,13(3)
Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO3−) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m2) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO3− (HN: 2 × 70 mL BJ/day) (2) medium-NO3− (MN: 70 mL BJ/day), (3) low-NO3− (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO3−-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO3− intake, and by measuring NO3− and NO2− concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO3− dose and the increase in plasma and urinary NO3− concentration (R2 = 0.71, p < 0.001 and R2 = 0.46 p < 0.001, respectively), but relationships between NO3− dose and changes in salivary NO3− and NO2− were non-linear (R2 = 0.35, p = 0.002 and R2 = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults. 相似文献
75.
Katharina Voigt Emily Giddens Romana Stark Emma Frisch Neda Moskovsky Naomi Kakoschke Julie C. Stout Mark A. Bellgrove Zane B. Andrews Antonio Verdejo-Garcia 《Nutrients》2021,13(6)
Food homeostatic states (hunger and satiety) influence the cognitive systems regulating impulsive responses, but the direction and specific mechanisms involved in this effect remain elusive. We examined how fasting, and satiety, affect cognitive mechanisms underpinning disinhibition using a novel framework and a gamified test-battery. Thirty-four participants completed the test-battery measuring three cognitive facets of disinhibition: attentional control, information gathering and monitoring of feedback, across two experimental sessions: one after overnight fasting and another after a standardised meal. Homeostatic state was assessed using subjective self-reports and biological markers (i.e., blood-derived liver-expressed antimicrobial protein 2 (LEAP-2), insulin and leptin). We found that participants who experienced greater subjective hunger during the satiety session were more impulsive in the information gathering task; results were not confounded by changes in mood or anxiety. Homeostatic state did not significantly influence disinhibition mechanisms linked to attentional control or feedback monitoring. However, we found a significant interaction between homeostatic state and LEAP-2 on attentional control, with higher LEAP-2 associated with faster reaction times in the fasted condition only. Our findings indicate lingering hunger after eating increases impulsive behaviour via reduced information gathering. These findings identify a novel mechanism that may underpin the tendency to overeat and/or engage in broader impulsive behaviours. 相似文献
76.
BackgroundPerson‐centred care implies a change in interaction between care professionals and patients where patients are not passive recipients but co‐producers of care. The interactional practices of person‐centred care remain largely unexplored.ObjectiveThis study focuses on the analysis of disagreements, which are described as an important part in the co‐production of knowledge in interaction.DesignA qualitative exploratory study using conversation analysis.Setting and participantsData were collected from a nurse‐led person‐centred intervention in a hospital outpatient setting. Interactions between adult patients with irritable bowel syndrome (n = 17) and a registered nurse were audio‐recorded. COREQ guidelines were applied.ResultsDisagreements were found after demonstration of the nurse''s or patients’ respective professional or personal knowledge. Disagreements were also evident when deciding on strategies for self‐management. Although negotiations between opposing views of the nurse and patient were seen as important, the patient generally claimed final authority both in knowing how IBS is perceived and in the right to choose self‐management strategies. The nurse generally oriented towards patient authority, but instances of demonstration of nurse authority despite patient resistance were also found.Discussion and conclusionsThis study provides information on how co‐production of knowledge and decisions occur in the context of a person‐centred care intervention. Negotiations between nurse and patient views require a flexible approach to communication, adapting interaction to each context while bearing in mind the patients having the final authority. To facilitate co‐production, the patient''s role and responsibilities in interaction should be explicitly stated. 相似文献
77.
Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice
José Valdés-Fernández Tania López-Martínez Purificación Ripalda-Cemboráin Isabel A Calvo Borja Sáez Juan Antonio Romero-Torrecilla Javier Aldazabal Emma Muiños-López Verónica Montiel Josune Orbe José Antonio Rodríguez José Antonio Páramo Felipe Prósper Froilán Granero-Moltó 《Journal of bone and mineral research》2021,36(11):2203-2213
The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
78.
79.
Dadi Helgason Solveig Helgadottir Anders Ahlsson Jarmo Gunn Vibeke Hjortdal Emma C. Hansson Anders Jeppsson Ari Mennander Shahab Nozohoor Igor Zindovic Christian Olsson Stefan Orri Ragnarsson Martin I. Sigurdsson Arnar Geirsson Tomas Gudbjartsson 《The Annals of thoracic surgery》2021,111(4):1292-1298
80.
Josefine Jnsson Kristina M. Renault Sonia García-Calzn Alexander Perfilyev Angela C. Estampador Kirsten Nrgaard Mads Vendelbo Lind Allan Vaag Line Hjort Kim F. Michaelsen Emma Malchau Carlsen Paul W. Franks Charlotte Ling 《Diabetes》2021,70(4):854
Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth. 相似文献